Improving Neural Spike Sorting Performance Using Template Enhancement

This paper presents a novel method for improving the performance of template matching in neural spike sorting for similar shaped spikes, without increasing computational complexity. Mean templates for similar shaped spikes are enhanced to emphasise distinguishing features. Template optimisation is based on the variance of sample distributions. Improved spike sorting performance is demonstrated on simulated neural recordings with two and three neuron spike shapes. The method is designed for implementation on a Next Generation Neural Interface (NGNI) device at Imperial College London

Possibilities offered by implantable miniaturized cuff-electrodes for insect neurophysiology

AbstractRecent advances in microsystems technology led to a miniaturization of cuff-electrodes, which suggests these electrodes not just for long-term neuronal recordings in mammalians, but also in medium-sized insects. In this study we investigated the possibilities offered by cuff-electrodes for neuroethology using insects as a model organism. The implantation in the neck of a tropical bushcricket resulted in high quality extracellular nerve recordings of different units responding to various acoustic, vibratory, optical and mechanical stimuli. In addition, multi-unit nerve activity related to leg movements was recorded in insects walking on a trackball. A drawback of bi-polar nerve recordings obtained during tethered flight was overlay of nerve activity with large amplitude muscle potentials. Interestingly, cuff-electrode recordings were robust to withstand walking and flight activity so that good quality nerve recordings were possible even three days after electrode implantation. Recording multi-unit nerve activity in intact insects required an elaborate spike sorting algorithm in order to discriminate neuronal units responding to external stimuli from background activity. In future, a combination of miniaturized cuff-electrodes and light-weight amplifiers equipped with a wireless transmitter will allow the investigation of neuronal processes underlying natural behavior in freely moving insects. By this means cuff-electrodes may contribute to the development of realistic neuronal models simulating neuronal processes underlying natural insect behavior, such like mate choice and predator avoidance

Resource efficient on-node spike sorting

Current implantable brain-machine interfaces are recording multi-neuron activity by utilising multi-channel, multi-electrode micro-electrodes. With the rapid increase in recording capability has come more stringent constraints on implantable system power consumption and size. This is even more so with the increasing demand for wireless systems to increase the number of channels being monitored whilst overcoming the communication bottleneck (in transmitting raw data) via transcutaneous bio-telemetries. For systems observing unit activity, real-time spike sorting within an implantable device offers a unique solution to this problem. However, achieving such data compression prior to transmission via an on-node spike sorting system has several challenges. The inherent complexity of the spike sorting problem arising from various factors (such as signal variability, local field potentials, background and multi-unit activity) have required computationally intensive algorithms (e.g. PCA, wavelet transform, superparamagnetic clustering). Hence spike sorting systems have traditionally been implemented off-line, usually run on work-stations. Owing to their complexity and not-so-well scalability, these algorithms cannot be simply transformed into a resource efficient hardware. On the contrary, although there have been several attempts in implantable hardware, an implementation to match comparable accuracy to off-line within the required power and area requirements for future BMIs have yet to be proposed. Within this context, this research aims to fill in the gaps in the design towards a resource efficient implantable real-time spike sorter which achieves performance comparable to off-line methods. The research covered in this thesis target: 1) Identifying and quantifying the trade-offs on subsequent signal processing performance and hardware resource utilisation of the parameters associated with analogue-front-end. Following the development of a behavioural model of the analogue-front-end and an optimisation tool, the sensitivity of the spike sorting accuracy to different front-end parameters are quantified. 2) Identifying and quantifying the trade-offs associated with a two-stage hybrid solution to realising real-time on-node spike sorting. Initial part of the work focuses from the perspective of template matching only, while the second part of the work considers these parameters from the point of whole system including detection, sorting, and off-line training (template building). A set of minimum requirements are established which ensure robust, accurate and resource efficient operation. 3) Developing new feature extraction and spike sorting algorithms towards highly scalable systems. Based on waveform dynamics of the observed action potentials, a derivative based feature extraction and a spike sorting algorithm are proposed. These are compared with most commonly used methods of spike sorting under varying noise levels using realistic datasets to confirm their merits. The latter is implemented and demonstrated in real-time through an MCU based platform.Open Acces

Noise Characterization, Modeling, and Reduction for In Vivo Neural Recording

Studying signal and noise properties of recorded neural data is critical in developing more efficient algorithms to recover the encoded information. Important issues exist in this research including the variant spectrum spans of neural spikes that make it difficult to choose a globally optimal bandpass filter. Also, multiple sources produce aggregated noise that deviates from the conventional white Gaussian noise. In this work, the spectrum variability of spikes is addressed, based on which the concept of adaptive bandpass filter that fits the spectrum of individual spikes is proposed. Multiple noise sources have been studied through analytical models as well as empirical measurements. The dominant noise source is identified as neuron noise followed by interface noise of the electrode. This suggests that major efforts to reduce noise from electronics are not well spent. The measured noise from in vivo experiments shows a family of 1/f^x spectrum that can be reduced using noise shaping techniques. In summary, the methods of adaptive bandpass filtering and noise shaping together result in several dB signal-to-noise ratio (SNR) enhancement

From End to End: Gaining, Sorting, and Employing High-Density Neural Single Unit Recordings

The meaning behind neural single unit activity has constantly been a challenge, so it will persist in the foreseeable future. As one of the most sourced strategies, detecting neural activity in high-resolution neural sensor recordings and then attributing them to their corresponding source neurons correctly, namely the process of spike sorting, has been prevailing so far. Support from ever-improving recording techniques and sophisticated algorithms for extracting worthwhile information and abundance in clustering procedures turned spike sorting into an indispensable tool in electrophysiological analysis. This review attempts to illustrate that in all stages of spike sorting algorithms, the past 5 years innovations' brought about concepts, results, and questions worth sharing with even the non-expert user community. By thoroughly inspecting latest innovations in the field of neural sensors, recording procedures, and various spike sorting strategies, a skeletonization of relevant knowledge lays here, with an initiative to get one step closer to the original objective: deciphering and building in the sense of neural transcript

Real-time neural signal processing and low-power hardware co-design for wireless implantable brain machine interfaces

Intracortical Brain-Machine Interfaces (iBMIs) have advanced significantly over the past two decades, demonstrating their utility in various aspects, including neuroprosthetic control and communication. To increase the information transfer rate and improve the devices’ robustness and longevity, iBMI technology aims to increase channel counts to access more neural data while reducing invasiveness through miniaturisation and avoiding percutaneous connectors (wired implants). However, as the number of channels increases, the raw data bandwidth required for wireless transmission also increases becoming prohibitive, requiring efficient on-implant processing to reduce the amount of data through data compression or feature extraction. The fundamental aim of this research is to develop methods for high-performance neural spike processing co-designed within low-power hardware that is scaleable for real-time wireless BMI applications. The specific original contributions include the following: Firstly, a new method has been developed for hardware-efficient spike detection, which achieves state-of-the-art spike detection performance and significantly reduces the hardware complexity. Secondly, a novel thresholding mechanism for spike detection has been introduced. By incorporating firing rate information as a key determinant in establishing the spike detection threshold, we have improved the adaptiveness of spike detection. This eventually allows the spike detection to overcome the signal degradation that arises due to scar tissue growth around the recording site, thereby ensuring enduringly stable spike detection results. The long-term decoding performance, as a consequence, has also been improved notably. Thirdly, the relationship between spike detection performance and neural decoding accuracy has been investigated to be nonlinear, offering new opportunities for further reducing transmission bandwidth by at least 30% with minor decoding performance degradation. In summary, this thesis presents a journey toward designing ultra-hardware-efficient spike detection algorithms and applying them to reduce the data bandwidth and improve neural decoding performance. The software-hardware co-design approach is essential for the next generation of wireless brain-machine interfaces with increased channel counts and a highly constrained hardware budget. The fundamental aim of this research is to develop methods for high-performance neural spike processing co-designed within low-power hardware that is scaleable for real-time wireless BMI applications. The specific original contributions include the following: Firstly, a new method has been developed for hardware-efficient spike detection, which achieves state-of-the-art spike detection performance and significantly reduces the hardware complexity. Secondly, a novel thresholding mechanism for spike detection has been introduced. By incorporating firing rate information as a key determinant in establishing the spike detection threshold, we have improved the adaptiveness of spike detection. This eventually allows the spike detection to overcome the signal degradation that arises due to scar tissue growth around the recording site, thereby ensuring enduringly stable spike detection results. The long-term decoding performance, as a consequence, has also been improved notably. Thirdly, the relationship between spike detection performance and neural decoding accuracy has been investigated to be nonlinear, offering new opportunities for further reducing transmission bandwidth by at least 30\% with only minor decoding performance degradation. In summary, this thesis presents a journey toward designing ultra-hardware-efficient spike detection algorithms and applying them to reduce the data bandwidth and improve neural decoding performance. The software-hardware co-design approach is essential for the next generation of wireless brain-machine interfaces with increased channel counts and a highly constrained hardware budget.Open Acces

A Wavelet-Based Method for Action Potential Detection from Extracellular Neural Signal Recording with Low Signal-to-Noise Ratio

We present a method for the detection of action potentials, an essential first step in the analysis of extracellular neural signals. The low signal-to-noise ratio (SNR) and similarity of spectral characteristic between the target signal and background noise are obstacles to solving this problem and, thus, in previous studies on experimental neurophysiology, only action potentials with sufficiently large amplitude have been detected and analyzed. In order to lower the level of SNR required for successful detection, we propose an action potential detector based on a prudent combination of wavelet coefficients of multiple scales and demonstrate its performance for neural signal recording with varying degrees of similarity between signal and noise. The experimental data include recordings from the rat somatosensory cortex, the giant medial nerve of crayfish, and the cutaneous nerve of bullfrog. The proposed method was tested for various SNR values and degrees of spectral similarity. The method was superior to the Teager energy operator and even comparable to or better than the optimal linear detector. A detection ratio higher than 80% at a false alarm ratio lower than 10% was achieved, under an SNR of 2.35 for the rat cortex data where the spectral similarity was very high.This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the Nano Bioelectronics and Systems Research Center

Automatic Detection and Classification of Neural Signals in Epilepsy

The success of an epilepsy treatment, such as resective surgery, relies heavily on the accurate identification and localization of the brain regions involved in epilepsy for which patients undergo continuous intracranial electroencephalogram (EEG) monitoring. The prolonged EEG recordings are screened for two main biomarkers of epilepsy: seizures and interictal spikes. Visual screening and quantitation of these two biomarkers in voluminous EEG recordings is highly subjective, labor-intensive, tiresome and expensive. This thesis focuses on developing new techniques to detect and classify these events in the EEG to aid the review of prolonged intracranial EEG recordings. It has been observed in the literature that reliable seizure detection can be made by quantifying the evolution of seizure EEG waveforms. This thesis presents three new computationally simple non-patient-specific (NPS) seizure detection systems that quantify the temporal evolution of seizure EEG. The first method is based on the frequency-weighted-energy, the second method on quantifying the EEG waveform sharpness, while the third method mimics EEG experts. The performance of these new methods is compared with that of three state-of-the-art NPS seizure detection systems. The results show that the proposed systems outperform these state-of-the-art systems. Epilepsy therapies are individualized for numerous reasons, and patient-specific (PS) seizure detection techniques are needed not only in the pre-surgical evaluation of prolonged EEG recordings, but also in the emerging neuro-responsive therapies. This thesis proposes a new model-based PS seizure detection system that requires only the knowledge of a template seizure pattern to derive the seizure model consisting of a set of basis functions necessary to utilize the statistically optimal null filters (SONF) for the detection of the subsequent seizures. The results of the performance evaluation show that the proposed system provides improved results compared to the clinically-used PS system. Quantitative analysis of the second biomarker, interictal spikes, may help in the understanding of epileptogenesis, and to identify new epileptic biomarkers and new therapies. However, such an analysis is still done manually in most of the epilepsy centers. This thesis presents an unsupervised spike sorting system that does not require a priori knowledge of the complete spike data

Implantable Asynchronous Epilectic Seizure Detector

RÉSUMÉ Plusieurs algorithmes de détection à faible consommation ont été proposés pour le traitement de l'épilepsie focale. La gestion de l'énergie dans ces microsystèmes est une question importante qui dépend principalement de la charge et de la décharge des capacités parasites des transistors et des courants de court-circuit pendant les commutations. Dans ce mémoire, un détecteur asynchrone de crise pour le traitement de l'épilepsie focale est présenté. Ce système fait partie d'un dispositif implantable intégré pour stopper la propagation de la crise. L'objectif de ce travail est de réduire la dissipation de puissance en évitant les transitions inutiles de signaux grâce à la technique du « clock tree » ; en conséquence, les transistors ne changent pas d'état transitoire dans ce mode d'économie d'énergie (période de surveillance des EEG intracrâniens), sauf si un événement anormal est détecté. Le dispositif intégré proposé comporte un bio-amplificateur en amont (front-end) à faible bruit, un processeur de signal numérique et un détecteur. Un délai variable et quatre détecteurs de fenêtres de tensions variables en parallèles sont utilisés pour extraire de l’information sur le déclenchement des crises. La sensibilité du détecteur est améliorée en optimisant les paramètres variables en fonction des activités de foyers épileptiques de chaque patient lors du début des crises. Le détecteur de crises asynchrone proposé a été implémenté premièrement en tant que prototype sur un circuit imprimé circulaire, ensuite nous l’avons intégré sur une seule puce dans la technologie standard CMOS 0.13μm. La puce fabriquée a été validée in vitro en utilisant un total de 34 enregistrements EEG intracrâniens avec la durée moyenne de chaque enregistrement de 1 min. Parmi ces jeux de données, 15 d’entre eux correspondaient à des enregistrements de crises, tandis que les 19 autres provenaient d’enregistrements variables de patients tels que de brèves crises électriques, des mouvements du corps et des variations durant le sommeil. Le système proposé a réalisé une performance de détection précise avec une sensibilité de 100% et 100% de spécificité pour ces 34 signaux icEEG enregistrés. Le délai de détection moyen était de 13,7 s après le début de la crise, bien avant l'apparition des manifestations cliniques, et une consommation d'énergie de 9 µW a été obtenue à partir d'essais expérimentaux.----------ABSTRACT Several power efficient detection algorithms have been proposed for treatment of focal epilepsy. Power management in these microsystems is an important issue which is mainly dependent on charging and discharging of the parasitic capacitances in transistors and short-circuit currents during switching. In this thesis, an asynchronous seizure detector for treatment of the focal epilepsy is presented. This system is part of an implantable integrated device to block the seizure progression. The objective of this work is reducing the power dissipation by avoiding the unnecessary signal transition and clock tree; as a result, transistors do not change their transient state in power saving mode (icEEG monitoring period) unless an abnormal event detected. The proposed integrated device contains a low noise front-end bioamplifier, a digital signal processor and a detector. A variable time frame and four concurrent variable voltage window detectors are used to extract seizure onset information. The sensitivity of the detector is enhanced by optimizing the variable parameters based on specific electrographic seizure onset activities of each patient. The proposed asynchronous seizure detector was first implemented as a prototype on a PCB and then integrated in standard 0.13 μm CMOS process. The fabricated chip was validated offline using a total of 34 intracranial EEG recordings with the average time duration of 1 min. 15 of these datasets corresponded to seizure activities while the remaining 19 signals were related to variable patient activities such as brief electrical seizures, body movement, and sleep patterns. The proposed system achieved an accurate detection performance with 100% sensitivity and 100 % specificity for these 34 recorded icEEG signals. The average detection delay was 13.7 s after seizure onset, well before the onset of the clinical manifestations. Finally, power consumption of the chip is 9 µW obtained from experimental tests